Laminar flow droplet generator device and methods of use

ABSTRACT

A piezoelectric ejector device is provided which is designed to minimize the intake of air into the device upon actuation by providing for laminar flow of the fluid. In an ejector mechanism that includes a generator plate and a piezoelectric actuator operable to directly or indirectly oscillate the generator plate, at a frequency to generate a directed stream of droplets of fluid, the generator plate includes a fluid facing surface, a droplet ejection surface, and a plurality of holes formed through its thickness between the surfaces. The plurality of holes are configured so as to minimize airflow through the plurality of openings from the droplet ejection surface to the fluid facing surface during generation of the directed stream of droplets by configuring the shape of the holes to minimize turbulence.

RELATED APPLICATIONS

The present application claims the benefit of the filing date of U.S.Patent Application Nos. 61/646,721, filed May 14, 2012, entitled“Ejector Mechanism, Ejector Device and Methods of Use” and 61/722,600filed Nov. 5, 2012, entitled “Laminar Flow Droplet Generator Device andMethods of Use”, the contents of which are herein incorporated byreference in their entireties.

BACKGROUND OF THE INVENTION

Using spray devices to administer products in the form of mists orsprays is an area with large potential for safe, easy-to-use products.An important area where spray devices are needed is in delivery of eyemedications. However, a major challenge in providing such a device is toprovide consistent and accurate delivery of suitable doses. In addition,a multi-dose spray device may become exposed to possible contaminationas a result of interaction with a non-sterile outside environment.

Accordingly, there is a need for a delivery device that delivers safe,suitable, and repeatable dosages to a subject for ophthalmic, topical,oral, nasal, or pulmonary use.

SUMMARY OF THE INVENTION

The present disclosure relates, in part, to an ejector mechanism,ejector device and method of delivering safe, suitable, and repeatabledosages to a subject for ophthalmic, topical, oral, nasal, or pulmonaryuse. The present disclosure relates to an ejector device and fluiddelivery system capable of delivering a defined volume of the fluid inthe form of a directed stream of droplets having properties that affordadequate and repeatable high percentage deposition of droplets uponapplication.

According to the disclosure, a piezoelectric ejector device is providedwhich is designed to minimize the intake of air into the device uponactuation, as explained in further detail herein. The ejector mechanismmay include a generator plate and a piezoelectric actuator operable todirectly or indirectly oscillate the generator plate, at a frequency togenerate a directed stream of droplets of fluid. The generator plateincludes a fluid facing surface, a droplet ejection surface, and aplurality of openings formed through its thickness between the surfaces.According to the disclosure, the generator plate and its plurality ofopenings are configured so as to minimize airflow through the pluralityof openings from the droplet ejection surface to the fluid facingsurface during oscillation by promoting laminar flow of liquid as itpasses from the fluid facing surface to the droplet ejection surface.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows illustrative turbulent and laminar flow, in accordance withaspects of the disclosure;

FIG. 2 shows exemplary generator plate opening geometries, resulting inturbulent flow (left) and laminar flow (right), in accordance withaspects of the disclosure;

FIG. 3 shows exemplary generator plate opening geometries, resulting inturbulent flow (left) and laminar flow (right), in accordance withaspects of the disclosure;

FIG. 4 illustrates exemplary curvatures of laminar flow generator plateopenings, in accordance with aspects of the disclosure;

FIG. 5 illustrates exemplary curvatures of laminar flow generator plateopenings, in accordance with aspects of the disclosure;

FIG. 6 illustrates entrance length parameters of a pipe/opening, inaccordance with embodiments of the disclosure;

FIG. 7 shows a plot of initial turbulent entry length as a function ofReynold's number, in accordance with aspects of the disclosure;

FIG. 8 illustrates one embodiment of a non-laminar NiCo ejector inoperation according to the disclosure;

FIG. 9 illustrates another embodiment of a laminar NiCo ejector inoperation according to the disclosure;

FIG. 10 illustrates one embodiment of a non-laminar PEEK ejector inoperation according to the disclosure;

FIG. 11 illustrates another embodiment of a laminar PEEK ejector inoperation, according to the disclosure;

FIGS. 12-14 show three-dimensional views of ejector surfaces ofdifferent embodiments of droplet generator plates;

FIG. 15 shows a side view of a droplet generator plate hole according tothe disclosure;

FIG. 16 shows a cross-sectional view of an ejector device, in accordancewith aspects of the disclosure;

FIGS. 17A and B show cross-sectional views of an activated ejector platefor the ejector device of FIG. 16;

FIG. 18 is plan view of one embodiment of an ejector mechanism of thedisclosure;

FIG. 19 is a dismantled view of an symmetric ejector mechanism of thedisclosure, and

FIG. 20 is a plan view of a symmetric ejector mechanism of thedisclosure.

DETAILED DESCRIPTION

The present disclosure generally relates to piezoelectric ejectordevices useful, e.g., in the delivery of fluids, such as ophthalmicfluids to the eye. The ejector device may include an ejector assemblyincluding an ejector mechanism and a fluid supply. In certain aspects,the ejector mechanism may comprise a piezoelectric actuator and adroplet generator plate, which are operable to generate a directedstream of droplets of fluid when the actuator is actuated to directly orindirectly oscillate the generator plate. Fluid includes withoutlimitation, suspensions or emulsions which have viscosities in a rangecapable of droplet formation using an ejector mechanism.

Piezoelectric droplet generation and flow in micro-channels depends on acomplex interaction between liquid flow through micro-orifices,fluid-surface interactions, exit orifice diameter, entrant cavitygeometry, capillary tube length, ejector material mechanical properties,amplitude and phase of the mechanical displacement, and frequency ofdisplacement of ejector plate. Moreover, fluid properties such asviscosity, density and surface energy play major roles in dropletformation. In accordance with certain aspects of the disclosure, novelejector hole structures and geometries that optimize droplet generationdynamics and microfluidic flow have been developed. For example, certainembodiments related to computer controlled laser micromachining thatprovides accurate control of the three-dimensional topography of theejector surface and nozzle geometry. This provides independent controlover fluid velocity amplification, resistance, turbulence and valving ofhigh viscosity fluids.

According to the present disclosure, a piezoelectric ejector device isprovided which is designed to minimize the intake of air into the deviceupon actuation, as explained in further detail herein. As discussedabove, the ejector mechanism includes a generator plate and apiezoelectric actuator operable to directly or indirectly oscillate thegenerator plate, at a frequency to generate a directed stream ofdroplets of fluid. The generator plate includes a fluid facing surface,a droplet ejection surface, and a plurality of openings formed throughits thickness between the surfaces. As described in the variousembodiments disclosed in the present disclosure, the generator plate andits plurality of openings are configured so as to minimize airflowthrough the plurality of openings from the droplet ejection surface tothe fluid facing surface during generation of the directed stream ofdroplets. As explained herein, minimizing of airflow results, in part,in laminar flow of the directed stream of droplets. By way ofbackground, but without intending to be limited by theory, intake of airinto the ejector device during operation can result in unpredictablebehavior within the device that may not only alter the operation of thedevice but in many cases may result in failure. Again, without beinglimiting, the vibrating pump-like action of the ejection area of theejector mechanism of the disclosure creates pressure gradients that areboth in the direction of droplet ejection as well as in the oppositedirection of ejection. When the pressure gradient is aligned opposite tothe direction of ejection, air within the surrounding region has anopportunity to move into the lower pressure area behind the active areaby passing though the ejector openings.

However, the intake of air through the ejector openings may be preventedby the presence of fluid behind the ejector openings, thereby blockingthe air from entering the system. In certain instances, air may enterthe system through paths formed from gaps created during processes thatinterfere with proper symmetric fill conditions. These processes createchaotic turbulent regions between the liquid and air, which allowoverpressures to occur that encapsulate the air that has moved into theopenings to create bubbles.

One way in which air can enter the system by overcoming the resistanceof generator plate openings is by fluid turbulence on the fluid side ofthe ejector mechanism created from an abrupt transition in fluid flow,for example, as fluid enters the fluid reservoir side of the generatorplate. Rapidly moving fluid experiences a sudden change in flow due to alarge and sudden change in slope at a transition point. With referenceto FIG. 1A, the fluid “overshoots” the transition point region andshears the fluid below resulting in vortices or “vena contracta” whichare regions of nonzero vorticity. As shown in FIG. 1A, this results in avorticity ω (which is a function of fluid velocity) to have a valuegreater than 0. In contrast, when the transition is gradual, as shown inFIG. 1B, the shearing does not take place and vortices are avoided(vorticity ω=0).

With reference to FIG. 2, the generator plate on the left shows anabrupt transition, resulting in turbulent flow and a chaotic spray,which allows outside air to enter into the system via the generatorplate openings during operation. The illustrated generator plate openingcomprises a shape with a large transition from fluid reservoir side tothe droplet ejection side, which encourages the formation of vorticesleading to broken flow and the formation of gaps within the opening. Incontrast, the generator plate opening on the right has a gradual changein slope from the fluid reservoir side to the droplet ejection side,resulting in laminar flow and efficient spray.

The present disclosure generally relates to ejector devices useful,e.g., in the delivery of fluid for ophthalmic, topical, oral, nasal, orpulmonary use, more particularly, for use in the delivery of ophthalmicfluid to the eye. In one embodiment, the ejector device includes anejector assembly including an ejector mechanism which generates acontrollable stream of droplets of fluid. The ejector mechanism may be acharge isolated mechanism. Fluid includes, without limitation,suspensions or emulsions which have viscosities in a range capable ofdroplet formation using an ejector mechanism. Fluids may includepharmaceutical and medicament products.

As explained in further detail herein, the ejector mechanism may form adirected stream of droplets, which may be directed toward a target. Thedroplets may be formed in a distribution of sizes, each distributionhaving an average droplet size. The average droplet size may be in therange of about 15 microns to over 400 microns, greater than 20 micronsto about 400 microns, about 20 microns to about 80 microns, about 25microns to about 75 microns, about 30 microns to about 60 microns, about35 microns to about 55 microns, about 20 microns to about 200 microns,about 100 microns to about 200 microns, etc. However, the averagedroplet size may be as large as 2500 microns, depending on the intendedapplication. Further, the droplets may have an average initial velocityof about 0.5 m/s to about 100 m/s, e.g., about 0.5 m/s to about 20,e.g., 0.5 to 10 m/s, about 1 m/s to about 5 m/s, about 1 m/s to about 4m/s, about 2 m/s, etc. As used herein, the ejecting size and the initialvelocity are the size and initial velocity of the droplets when thedroplets leave the ejector plate. The stream of droplets directed at atarget will result in deposition of a percentage of the mass of thedroplets including their composition onto the target.

As described herein, the ejector device and ejector mechanism of thedisclosure may be configured to eject a fluid of generally low torelatively high viscosity as a stream of droplets. By way of example,fluids suitable for use by the ejector device can have very lowviscosities, e.g., as with water at 1 cP, or less, e.g. 0.3 cP. Thefluid may additionally have viscosities in ranges up to 600 cP. Moreparticularly, the fluid may have a viscosity range of about 0.3 to 100cP, 0.3 to 50 cP, 0.3 to 30 cP, 1 cP to 53 cP, etc. In someimplementations, the ejection device may be used to eject a fluid havinga relatively high viscosity as a stream of droplets, e.g., a fluidhaving a viscosity above 1 cP, ranging from about 1 cP to about 600 cP,about 1 cP to about 200 cP, about 1 cP to about 100 cP, about 10 cP toabout 100 cP, etc. In some implementations, solutions or medicationshaving a suitable viscosity and surface tensions can be directly used inthe reservoir without modification. In other implementations, additionalmaterials may be added to adjust the fluid parameter.

Droplets may be formed by an ejector mechanism from fluid contained in areservoir coupled to the charge isolated ejector mechanism. The chargeisolated ejector mechanism and reservoir may be disposable or reusable,and the components may be packaged in a housing of an ejector device,such as those described in U.S. Provisional Application Nos. 61/569,739,61/636,559, 61/636,565, 61/636,568, 61/642,838, 61/642,867, 61/643,150and 61/584,060, and in U.S. patent application Ser. Nos. 13/184,446,13/184,468 and 13/184,484, the contents of which are incorporated hereinby reference. More particularly, exemplary ejector devices and ejectormechanism are illustrated in U.S. Application No. 61/569,739, filed Dec.12, 2011. entitled “Ejector Mechanism, Ejector Device, and Methods ofUse,” U.S. Application No. 61/636,565, filed Apr. 20, 2012, entitled“Centro-Symmetric Lead Free Ejector Mechanism, Ejector Device, andMethods of Use” and U.S. Application No. 61/591,786, filed Jan. 27,2012, entitled “High Modulus Polymeric Ejector Mechanism, EjectorDevice, And Methods Of Use,” each of which are herein incorporated byreference in their entirety.

In accordance with certain embodiments of the disclosure, the openingsof a generator plate of the disclosure are configured to have a shapewith a gradual slope of change from the fluid facing surface to thedroplet ejection surface. By way of background, without intending to belimited by theory, for fluid traveling in one dimension, the optimalfunction is linear (e.g., a pipe) and turbulence in the system isrelated to the Reynolds number, which is a function of the velocity,pipe diameter, density of fluid, and the viscosity of the fluid. TheReynolds number is a ratio of between inertial and viscous forces and isthus a dimensionless quantity. The flow is generally considered to belaminar when the Reynolds number is less than 2300 and is consideredturbulent for values above 4000. In the region between 2300 and 4000 theflow is considered to be “transitional” which means that both laminarand turbulent flows are possible.

${Re} = \frac{\rho\; v\; L}{\eta}$

Where Re is the Reynolds number,

ρ is the density of the fluid,

v is the velocity of the fluid,

L is the pipe diameter, and

η is the viscosity of the liquid.

To minimize the presence of turbulent regions formed from quicktransitions (steps) in the shape of an opening, the curvature may be afunction with a small second derivative. In accordance with one aspectof the disclosure, the second order curve which provides a minimum valuefor the second derivative is the shape of a circle whose function isshown below. In this regard, such curvatures comprise a shape having anexternal entry radius of curvature having a circular shape from thefluid facing surface to the droplet ejection surface.

$\frac{\mathbb{d}^{2}y}{\mathbb{d}x^{2}} = \frac{R^{2}}{\left( {R^{2} - x^{2}} \right)^{\frac{3}{2}}}$

Where R is the external radius of the curve.

With reference to FIG. 3, an opening having an external entry curvaturethat is not circular in shape is illustrated on the left. Such anopening exhibits a large sudden charge in the slope of the entrancecurve thereby promoting turbulent flow and chaotic spray, whichincreases the ability of outside air to enter the system. In contrast,on the right an opening in accordance with one embodiment of thedisclosure is illustrated, wherein the external entry radius ofcurvature comprises a circular shape, which results in laminar flow andminimizes the ability of outside air to enter the system.

Thus, laminar flow openings in accordance with the present disclosuremay be configured with gradually changing circular curvature, whichencourages laminar flow by minimizing voracity and eliminating thepresence of vortices. With reference to FIGS. 4 and 5, dimensions forconstructing laminar flow generator plate openings are provided inaccordance with aspects of the disclosure. In FIG. 4, the variables P,R, and D represent the pitch between openings, radius of curvature ofthe circular entry shape, and exit diameter of the opening,respectively. In FIG. 5, the additional variables De and σ are theentrance diameter, and the ratio of radius of curvature to exitdiameter, respectively.

In accordance with one aspect of the disclosure, the ratio σ (ratio ofsize of the radius of curvature to the size of the opening at thedroplet ejection surface) defines the proper conditions for constructinglaminar ejectors. In one embodiment, when the opening at the dropletejection surface is greater than about 40 μm a σ was chosen to be equalto or greater than about 2.5. In another embodiment, the ratio σ of sizeof the radius of curvature to the size of the opening at the dropletejection surface was chosen to be greater than about 5, when the openingat the droplet ejection surface was less than about 40 μm. It should benoted that the height or thickness of the mesh (defined by the generatorplate) is not necessarily limited to the dimensions illustrated in FIG.5 and can be larger or smaller than the dimensions shown.

According to another aspect, generator plate openings are configured soas to have an entrance length or generator plate thickness whichfacilitates the creation of a laminar flow region. By way of background,but without intending to be limited by theory, fluid entering a pipe(i.e., in the context of the present disclosure, fluid entering theopening of a generator plate) undergoes a period (length) in whichlaminar flow is not possible due to the initial boundary conditionsbetween the fluid and the surface of the pipe/opening. This isillustrated in FIG. 6. At the boundary, entry wall friction and viscousforces dominate for the fluid closest to the surface. Under “no-slip”boundary conditions, the fluid immediately at the wall has a tangentialvelocity of zero, and this bound layer exerts a viscous drag on theneighboring fluid layers, which drag force decreases with distance awayfrom the boundary layer. This causes layer dependent velocity regions toform in the fluid resulting in a non-uniform buildup of the finalviscous boundary layer at equilibrium. The distance it takes for theboundary layer to build up to constant layer is what is known as the“entrance length”. The “inviscid” region is the area where the effect ofviscosity is negligible. Once the flow has gone past the entrance lengthl_(e), laminar flow is possible (the laminar flow region is the regionwhere Poiseuille flow is established). Poiseuille flow is a flowcondition in which the velocity profile is parabolic. This distancel_(e) is a function of the Reynolds number Re and is given by theexpression l_(e)=(0.06vd)(Re) where v, d, and Re are the velocity of thefluid, diameter of the nozzle and Reynolds number, respectively. Therange of laminar flow as a function of Reynolds number applies for fluidthat has moved past this initial entrance length l_(e). In the chartbelow the values for both Reynolds number and entrance length werecalculated assuming a velocity of 2 m/s which was chosen based on theaverage droplet speed values calculated in one embodiment and asprovided by digital holographic microscopy (DHM) results for theembodiment, which measured the velocity for the active membrane withinthe range between 0.5-5 m/s. The ejector diameter hole size chosen forthe chart was 40 microns. Surface tension values were measured with agoniometer (contact angle analyzer), viscosity measurements wereperformed on a tuning fork “vibro” viscometer, and density measurementswere performed by measuring a known quantity of drug and weighing itusing a sensitive scale.

The results are shown in Table 1 below:

Surface Tension Dynamic Density le Drug (mN/m) Viscosity (cP) (g/mL) Re(microns) Saline 72.3 1.015 0.984 80 192 Latanoprost 28.4 1.088 0.982785.6 205 Restasis 40.7 17.48 0.949 4.4 11 Timolol 37.6 1.23 0.975 63.4152 Tropicamide 37.8 1.18 0.991 67.19 161 Water 72.8 1 0.9982 79.84 192

As was discussed above, the Reynolds number is a ratio between inertialand viscous forces and flow is generally considered to be laminar whenthe Reynolds number is less than 2300 and is considered turbulent forvalues above 4000. In the region between 2300 and 4000 the flow isconsidered to be “transitional” which means that both laminar andturbulent flows are possible. However, as is demonstrated by the resultsin Table 1 and as shown in FIG. 7 below, the Reynolds number is alsorelated to the entrance length l_(e).

FIG. 7 describes the entrance length of developing flow as a function ofReynolds numbers which have been calculated for a velocity range of 1-10m/s. As a result it was found that openings configured with entrancelength, le, (i.e., channel length) exceeding 150 micrometers are betterfor creating laminar conditions for 40 micron exit diameters, while for20 micron diameter holes, the entrance length le should exceed 100microns. Thus, when constructing laminar ejector openings, the thickness(i.e., channel length) of a laminar ejector may be determined, at leastin part, by the entrance diameter of the holes. In certain aspects, asufficient channel length to achieve laminar flow of an ejected fluid bythe time the fluid reaches the droplet ejection surface may be selected,as described herein.

FIGS. 8-11 are experimental results showing device performance to airintake during operation for ejectors having droplet generator plateswith regular, non-laminar flow holes, as opposed to droplet generatorplates with laminar flow holes. Droplet generator plates made from metal(NiCo, FIGS. 8 and 9) and polymer (PEEK, FIGS. 10 and 11) materials wereconsidered. In the FIG. 8 embodiment the actuator was operated at 107kHz and the droplet generator plate was provided with non-laminar flowholes. In the FIG. 9 embodiment the actuator was operated at 132 kHz andthe droplet generator plate was provided with laminar flow holes.

In the embodiment of FIG. 10, a droplet generator plate thickness of 100μm was used and the actuator was operated at 110 kHz. As in the FIG. 8embodiment, the holes in the droplet generator plate were regularnon-laminar flow holes. In the FIG. 11 embodiment, a droplet generatorplate thickness of 100 μm was used and the actuator was operated at 111kHz. As in the FIG. 9 embodiment, this droplet generator plate wasprovided with laminar flow holes. Thus for each material there is anexample of the performance of a non-laminar and laminar ejector designconstructed using the criterion described herein. The experiment wasperformed by mounting the device with a translucent reservoir filledwith water (water has a high surface tension as shown in the Table 1,which aids in the formation of air bubbles providing a worst casescenario for the test) and open to the atmosphere. The back of thereservoir was imaged during peak spray conditions to track the formationof air bubbles into the system. The mounting conditions are the same forall compared samples. It was found that the laminar designed ejectors(FIGS. 9 and 11) performed better than the non-laminar ejectors (FIGS. 8and 10) for all test. The laminar flow ejector design reduces the chanceof outside air from entering the system during operation by removing airgaps within the ejector openings (nozzles) by keeping them filled withfluid during spray.

The benefits from screening the system from additional air intakeinclude continued operation of the device without failure occurring fromexcess air in the system, which causes unpredictable changes of pressurewithin the system. The excess air can also contaminate the fluid withinthe system, which is undesirable when delivering pharmaceuticalcompositions, particularly low preservative and preservative freepharmaceutical compositions.

In additional aspects, in order to avoid build-up of liquid on theejection surface of the droplet generator plate, the ejection surfacemay also be configured to define trenches around at least a portion ofone or more ejector hole(s) as shown in FIGS. 12-14. The trenches maygenerally allow any fluid that may remain on the ejection surface topool in the trenches, rather than blocking the ejection holes. This canfurther reduce build-up of fluid on the ejection surface andinterference with droplet ejection.

To further counteract the effects of fluid beading on the ejectionsurface and the build-up of fluid, certain aspects further relate to theuse of coatings on the surface of the ejector plate, e.g., goldcoatings, silver coating, antimicrobial coatings, etc. In certainembodiments, coatings, e.g., gold coatings may be deposited on agenerator plate, e.g., a PEEK generator plate to modify the surface(higher surface energy to increase he hydrophilicity) so that fluidsflow more easily, to reduce fluid beading on the surface, etc.

In yet other aspects, the thickness of the droplet generator plate mayalso affect laminar flow parameters, with better laminar flow beingobtained from thicker plates with longer capillary tube length, whilealso affecting the oscillation of the plate, with thinner platesdisplaying better fluid ejection at higher frequencies. One embodimentwas found to work well with a capillary tube length of 125 μm. Thecapillary tube or channel 1500 in relation to the flute intake 1502 forlaminar flow is shown in FIG. 15.

The ejector assembly, which may include an ejector plate coupled to adroplet generator plate and a piezo actuator. FIG. 16, for example,shows one embodiment of an ejector assembly 1600 that includes anejector mechanism 1601 and reservoir 1620. The ejector mechanism 1601may include an oscillating plate mechanism or system with ejector plate1602 coupled to a generator plate or eliminating the generator plate andsimply defining a central droplet generator region or ejector region1632 that includes one or more openings 1626, which can be activated by(e.g. piezoelectric) actuator 1604. For ease of reference the dropletgenerator region 1632, whether it is integrally formed with the ejectorplate or coupled to the ejector plate as a separate droplet generatorplate, will be referred to interchangeably herein as a droplet generatorplate or droplet generator region. Actuator 1604 vibrates or otherwisedisplaces ejector plate 1602 to deliver fluid 1610 from reservoir 1620,either as single droplet 1612 (droplet on demand) from one or moreopenings 1626, or as stream of droplets 1612 ejected from one or moreopenings 1626, along direction 1614.

In some applications, ophthalmic fluid may be ejected toward an eye1616, for example in a human adult or child, or an animal. The fluid maycontain a pharmaceutical agent to treat a discomfort, condition, ordisease of the human or an animal, either in the eye or on a skinsurface, or in a nasal or pulmonary application.

The attachment of ejector 1604 to ejector plate 1602 may also affectoperation of ejection assembly 1600, and the creation of single dropletsor streams thereof. In the implementation of FIG. 16, for example,ejector 1604 (or a number of individual ejector components 1604) may becoupled to a peripheral region of ejector plate 1602, on surface 1622opposite reservoir 1620.

Central region 1630 of ejector plate 1602 includes droplet generatorregion 1632 with one or more openings 1626, through which fluid 1610passes to form droplets 1612. Ejection region (or droplet generator)1632 may occupy a portion of central region 1630, for example thecenter, or the ejection hole pattern of droplet generator region 1632may occupy substantially the entire area of central region 1630.Further, open region 1638 of reservoir housing 1608 may correspondsubstantially to the size of ejection region 1632, or open region 1638may be larger than ejection region 1632.

In this regard, the location of the openings may affect mass deposition,with ejection hole patterns near the center of central region 1630generally being preferred. Further, the configuration and location ofthe piezoelectric actuator 1604 may impact operation, including theinner and outer diameters of the ejector plate 1602, and the thicknessof the actuator 1604. In one embodiment a 19 mm outer diameter, 14 mminner diameter, 250 microns thick actuator may be used in a non-edgemounted application.

As shown in FIG. 16, ejector plate 1602 is disposed over or in fluidcommunication with reservoir 1620, containing fluid 1610. For example,reservoir housing 1608 can be coupled to ejector plate 1602 at aperipheral region 1646 of the first major surface 1625, using a suitableseal or coupling such as O-rings 1648 a to seal against reservoir wall1650. A portion 1644 of reservoir housing 1608 may also be provided inthe form of a collapsible bladder. However, the disclosure is not solimited, and any suitable bladder or reservoir may be used.

Prior to excitation, ejector assembly 1600 is configured in a restingstate. When a voltage is applied across electrodes 1606 a and 1606 b onopposite surfaces 1634 and 1636 of (e.g., piezoelectric) actuator 1604,ejector plate 1602 deflects to change between relatively more concaveshape 1700 and relatively more convex shape 1701, as shown in FIGS. 17Aand 17B, respectively.

When driven with an alternating voltage, actuator 1604 operates toreverse the convex and concave shapes 1700 and 1701 of ejector plate1602, inducing periodic movement (oscillation) of ejector plate 1602 inejection region (droplet generator) 1632. Droplets 1612 are formed atapertures or openings 1626, as described above, with the oscillatorymotion of ejection region 1632 causing one or more droplets 1612 to beejected along fluid delivery (ejection) direction 1614, for example in asingle-droplet (droplet on demand) application, or as a stream ofdroplets.

The drive voltage and frequency may be selected for improved performanceof the ejection mechanism, as described above. In certain embodimentsthe oscillation frequency of actuator 1604 may be selected at or near aresonance frequency of the fluid filled ejector mechanism, or at one ormore frequencies selected to oscillate ejector plate 1602 at such aresonance via superposition, interference, or resonant coupling.

When operated at or near a resonant frequency (for example, within thefull width at half maximum of a resonance), ejector plate 1602 mayamplify the displacement of ejector region (droplet generator) 1632,decreasing the relative power requirements of the actuator, as comparedto a direct-coupling design. The damping factor of the resonance system,including ejector plate 1602 and droplet generator 1632, may also beselected to be greater than the piezoelectric actuator input power, inorder to reduce fatigue and increase service life without substantialfailure.

Examples of ejector assemblies are illustrated in U.S. ProvisionalPatent Application No. 61/569,739, “Ejector Mechanism, Ejector Device,and Methods of Use,” filed Dec. 12, 2011, as incorporated by referenceherein. In one particular embodiment, ejector plate mechanism 1601 mayinclude a rotationally symmetric ejector plate 1602 coupled to agenerator plate-type actuator 1604, for example as shown in FIG. 18, andas described in U.S. Provisional Patent Application No. 61/636,565,“Centro-Symmetric Lead Free Ejector Mechanism, Ejector Device, andMethods of Use,” filed Apr. 20, 2012, also incorporated by referenceherein. However, the disclosure is not so limited.

In the particular configuration of FIG. 18, generator plate-typeactuator 1604 incorporates one or more individual piezoelectric devicesor other actuator elements, as described above, for driving rotationallysymmetric ejector plate 1602. Droplet generator plate 1632 includes apattern of openings 1626 in center region 1630, and is driven via theejector plate 1602 using a suitable drive signal generator circuit asdescribed below. Exemplary techniques for generating drive voltages areillustrated in U.S. Provisional Patent Application No. 61/647,359,“Methods, Drivers and Circuits for Ejector Devices and Systems,” filedMay 15, 2012, as incorporated by reference herein.

FIG. 19 is a dismantled view of symmetric ejector mechanism 1601. Inthis embodiment, ejector plate 1602 utilizes a discrete (separate)droplet generator plate 1632, as shown on the left and right of FIG. 19from the back (face down) surface 1625 and the front (face up) surface1622, respectively. Droplet generator plate 1632 is mechanically coupledto ejector plate 1602 in central aperture 1652, and includes a patternof openings 1626 configured to generate a stream of fluid droplets whendriven by generator-plate type actuator 1604, as described above.

FIG. 20 is a plan view of symmetric ejector mechanism 1601. Ejectormechanism 1601 includes ejector plate 1602 with mechanical couplings1604C to generator plate-type actuator 1604 and droplet generator plate1632 with a pattern of openings 1626 in central region 1630, asdescribed above. Ejector mechanism 1601 may be coupled to a fluidreservoir or other ejection device component via apertures 1651 intab-type mechanical coupling elements 1655, or using another suitableconnection as described above with respect to FIG. 16.

As shown in FIG. 20, ejector mechanism 1601 and ejector plate 1602 maybe defined by overall dimension 1654, for example about 21 mm, or in arange of about 10 mm or less to about 25 mm or more, depending uponapplication. Suitable materials for ejector plate 1602 and dropgenerator 1632 include, but are not limited to, flexible stress andfatigue-resistant metals such as stainless steel.

For orientation purposes, the different elements of ejector mechanism1601 as shown in FIGS. 18-20 may be described relative to the locationof fluid 1610 or reservoir 1620, as described above with respect to FIG.16. In general, the proximal elements of mechanism 1601 are locatedcloser to fluid reservoir 1620 and the distal elements are locatedfarther from fluid reservoir 1620, as defined along the droplet streamor ejection direction 1614.

The ejector assembly described herein may be incorporated into anejector device. Exemplary ejector devices are illustrated in U.S. patentapplication Ser. No. 13/184,484, filed Jul. 15, 2011, the contents ofwhich are herein incorporated by reference.

Many implementations of the invention have been disclosed. Thisdisclosure contemplates combining any of the features of oneimplementation with the features of one or more of the otherimplementations. For example, any of the ejector mechanisms, orreservoirs can be used in combination with any of the disclosed housingsor housing features, e.g., covers, supports, rests, lights, seals andgaskets, fill mechanisms, or alignment mechanisms. Further variations ofany of the elements of any of the embodiments herein are within thescope of ordinary skill and are contemplated by this disclosure. Suchvariations include selection of materials, coatings, or methods ofmanufacturing. Any of the electrical and electronic technology can beused with any of the implementations without limitation. Furthermore,any networking, remote access, subject monitoring, e-health, datastorage, data mining, or internet functionality with respect to datacaptured by the device, is applicable to any and all of theimplementations and can be practiced therewith. Further still,additional diagnostic functions, such as performance of tests ormeasurements of physiological parameter may be incorporated into thefunctionality of any of the implementations. Performance of glaucoma orother ocular tests can be performed by the devices as a part of theirdiagnostic functionality. Other methods of fabrication known in the artand not explicitly listed here can be used to fabricate, test, repair,or maintain the device. Furthermore, the device may include moresophisticated imaging or alignment mechanisms than those described inthe incorporated prior applications. For example, the device or base maybe equipped with or coupled to an iris or retina scanner to create aunique id to match a device to the user, and to delineate between eyes.Alternatively, the device or base may be coupled to or includesophisticated imaging devices for any suitable type of photography orradiology.

Although the foregoing describes various embodiments by way ofillustration and example, the skilled artisan will appreciate thatvarious changes and modifications may be practiced within the spirit andscope of the present application.

What is claimed is:
 1. A device for generating a directed stream ofdroplets, the device comprising: a housing; a reservoir disposed withinthe housing for receiving a volume of fluid; and an ejector mechanism influid communication with the reservoir and configured to generate thedirected stream of droplets of said fluid, the ejector mechanismcomprising a generator plate and a piezoelectric actuator; wherein thegenerator plate includes a fluid facing surface, a droplet ejectionsurface, and a plurality of openings formed through its thicknessbetween said surfaces; wherein the piezoelectric actuator is operable todirectly or indirectly oscillate the generator plate, at a frequency togenerate the directed stream of droplets of said fluid; and wherein theplurality of openings of the generator plate have a gradual slope ofchange from the fluid facing surface to the droplet ejection surface soas to provide an external entry radius of curvature having a circularshape thereby reducing airflow through the plurality of openings fromthe droplet ejection surface to the fluid facing surface duringgeneration of the directed stream of droplets to provide the fluid withlaminar flow as it passes through the openings.
 2. The device of claim1, wherein the intake from the fluid facing surface into each of theopenings defines a fluted intake providing a gradual transition from thefluid facing surface into the opening.
 3. The device of claim 1, whereinat the droplet ejection surface trench is defined around at least one ofthe openings.
 4. The device of claim 1, wherein the ratio of size of theradius of curvature to the size of the opening at the droplet ejectionsurface is: greater than about 2.5, when the opening at the dropletejection surface is greater than about 40 μm, or the ratio is greaterthan about 5, when the opening at the droplet ejection surface is lessthan about 40 μm.
 5. The device of claim 1, wherein each opening definesa fluted intake and a channel that extends to the droplet ejectionsurface, the channel being configured with sufficient length so as toachieve laminar flow of the fluid prior to the fluid reaching theejection surface.
 6. The device of claim 1, wherein said ejectormechanism further comprises an ejector plate coupled to the generatorplate and the piezoelectric actuator, the piezoelectric actuator beingoperable to oscillate the ejector plate, and thereby the generatorplate, at the frequency to generate the directed stream of droplets. 7.The device of claim 6, wherein the ejector plate has a central openregion aligned with the generator plate, and the piezoelectric actuatoris coupled to a peripheral region of the ejector plate so as not toobstruct the plurality of openings of the generator plate.
 8. The deviceof claim 7, wherein the plurality of openings of the generator plate aredisposed in a center region of the generator plate that is uncovered bythe piezoelectric actuator and aligned with the central open region ofthe ejector plate.
 9. The device of claim 7, wherein the generator platehas a reduced size relative to the ejector plate, and the size of thegenerator plate is determined, at least in part, by the area occupied bythe center region and the arrangement of the plurality of openings. 10.The device of claim 1, wherein the ejector mechanism is configured toeject the directed stream of droplets such that at least about 75% ofthe mass of the ejected droplets deposit on the target.
 11. The deviceof claim 1, wherein the ejector mechanism is configured to eject thedirected stream of droplets having an average ejected droplet diameterin the range of 20 to 400 microns.
 12. The device of claim 1, whereinthe ejecting mechanism is configured to eject the directed stream ofdroplets having an average initial ejected velocity in the range of 0.5m/s to 10 m/s.